Apoptotic Caspases Suppress Type I Interferon Production via the Cleavage of cGAS, MAVS, and IRF3

• Published in: Molecular cell Vol. 74; no. 1; pp. 19 - 31.e7
• Main Authors: Ning, Xiaohan, Wang, Yutao, Jing, Miao, Sha, Mengyin, Lv, Mengze, Gao, Pengfei, Zhang, Rui, Huang, Xiaojun, Feng, Ji-Ming, Jiang, Zhengfan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.04.2019
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Apoptosis; apoptotic caspase; Caspase 2 - genetics; Caspase 2 - metabolism; Caspase 3 - genetics; Caspase 3 - metabolism; Caspase 7 - genetics; Caspase 7 - metabolism; Caspase 9 - genetics; Caspase 9 - metabolism; caspase-3; caspase-7; Caspases - genetics; Caspases - metabolism; cGAS; cleavage; cytokines; DNA; encephalitis; Female; HEK293 Cells; HeLa Cells; homeostasis; Host-Pathogen Interactions; Humans; Immunity, Innate; immunologically silent; inflammasomes; innate immunity; Interferon Regulatory Factor-3 - genetics; Interferon Regulatory Factor-3 - metabolism; Interferon Type I - metabolism; interferons; IRF3; Male; MAVS; mice; Mice, Inbred C57BL; Nucleotidyltransferases - genetics; Nucleotidyltransferases - metabolism; RNA; Sendai virus - immunology; Sendai virus - pathogenicity; Signal Transduction; THP-1 Cells; type I-interferon; Vaccinia virus - immunology; Vaccinia virus - pathogenicity; Virus Diseases - enzymology; Virus Diseases - genetics; Virus Diseases - immunology; Virus Diseases - virology; virus infection; type I-interferon; cleavage; MAVS; innate immunity; IRF3; apoptotic caspase; cGAS; apoptosis; immunologically silent; virus infection

Viral infection triggers host defenses through pattern-recognition receptor-mediated cytokine production, inflammasome activation, and apoptosis of the infected cells. Inflammasome-activated caspases are known to cleave cyclic GMP-AMP synthase (cGAS). Here, we found that apoptotic caspases are criti...